During the past year, we have completed extensive analyses of the NCS R data and have published numerous papers on the following topics: the prevalence and correlates of bipolar spectrum disorder in the U.S. adult population; the impact of physical and mental disorder comorbidity on role disability; the prevalence, impact and patterns of comorbidity of migraine and tension-type headache in the U.S. general population, and the risk factors and correlates of substance use disorders in the general population. [unreadable] [unreadable] The major findings of this work that are relevant to our research are that there is a spectrum of expression of bipolar disorder in the population with evidence for clinical validity of sub-threshold bipolar disorder; comorbidity between bipolar disorder and other mental disorders is dramatically elevated such that nearly two-thirds of bipolars have a substance use disorder; using a novel analytic method that accounts for comorbidity, we estimated the comparative effects of common mental and physical conditions on role disability in the general population. After controlling for comorbidity, we found that mental conditions account for more than half as many disability days as all physical conditions at the population level; eighty-five percent of migraineurs in the general population have at least one other lifetime mental or physical disorder. Comorbidity explained more than half the role disability associated with migraine. [unreadable] [unreadable] The NCS-R data have also been applied to examine fundamental questions in the epidemiology of substance use disorders. Using the NCS-R and NCS1-2 panel data, our research group has worked over the past 18 months to examine fundamental questions in the epidemiology of substance use disorders. A first series of manuscripts addressed sociodemographic risk factors across diverse stages of alcohol (Kalaydjian et al, in press), tobacco (Dierker et al, 2008), and illicit substances (Swendsen et al., in press). These investigations provide highly novel information concerning the precise stages of the substance use trajectory that are most associated with population-based risk factors, knowledge that has direct implications for improving the precision of selective and indicated prevention strategies. A second series of manuscripts examined associations among categories of substances and associated disorders, including the manner in which particular substances may increase the risk of other types of substance use or disorders (e.g. the gateway hypothesis) and the degree to polysubstance use or abuse constitutes a risk factor for later dependence (Degenhardt et al., in press; Swendsen, under review). These studies indicate for the first time that gateway violations are largely unrelated to later dependence risk, but also that the use or abuse of any single substance considerably increases the risk of all other forms of substance dependence over the subsequent decade. Finally, two manuscripts examine the risk posed by comorbid psychopathology for the onset of substance use disorders (Swendsen, in preparation) and whether it would be cost-effective to prevent secondary substance dependence by large-scale interventions aimed at index mental disorders (Meyer et al, in press). The findings of these investigations demonstrate that, despite their frequent role in the onset of substance abuse and dependence, treating index mental disorders as a means reducing substance dependence would not be cost-effective relative to other prevention options. [unreadable] [unreadable] During the past few months, we have begun to examine the spectrum concept of mood disorders using a dimensional framework to characterize people with mania and/or depression. This work is being conducted with a team on international investigators who propose to modify the current diagnostic nomenclature by considering bipolar disorder and major depression as a spectrum of symptoms, duration, recurrence, and severity rather than as discrete categories. Our analyses clearly confirm that validity of the spectrum concept in a general population sample based on independent indices such as disability, impairment, family history, severity and patterns of comorbidity. [unreadable] [unreadable] Other work in progress includes evaluation of the role of family and marital factors in clinical severity, disability, and service use for mental disorders; comparison of the prevalence of bipolar spectrum disorder in the U.S. with comparable data from 20 other countries; and the significance of irritability as an index of bipolar disorder and major depression.